Patients with idiopathic membranous nephropathy are being studied to evaluate the efficacy and toxicities of the addition of intermittent cyclophosphamide to alternate day oral corticosteroid therapy. Efficacy will be judged by determinations of effective renal plasma flow, glomerular filtration rate and glomerular capillary wall permselectivity performed with dextran and urine protein (albumin and immunoglobulin) clearance techniques. Kidney biopsy morphology (including morphometric analysis) will be examined at the beginning and at the end of treatment as part of detailed studies of structure- function relationships and the efficacy of various therapeutic modalities. Patients with membranous nephropathy and 2 or more grams per day of proteinuria will be treated with alternate day prednisone and will be randomized to receive: a) no additional therapy (control group) (n=14), or b) intravenous pulse cyclophosphamide up to 1.0 gram per square meter body surface area every other month for 6 total doses (n=17). Analysis will include comparison of the number of favorable outcomes of glomerular function and pathology, as well as drug-related toxicities observed in each treatment group at the end of the 12 months of study. To date, the rates of renal outcomes are not significantly different in the groups receiving prednisone alone or prednisone plus intermittent cyclophosphamide. Eleven of 15 patients with impaired renal function at presentation (glomerular filtration rate [GFR] < 60 ml/min) showed an average 86% increase in GFR at 1 year. Urine protein excretion decreased > 50% in 14 patients, including 11 of 20 patients with severe proteinuria (> 8 gm/day). Treatment group assignment as well as other potentially important clinical and histologic prognostic factors did not predict change in GFR or change in urinary protein excretion rate. Long-term follow-up studies are in progress to determine the durability of the clinical responses, the incidence of relapse, the risk of progressive renal failure, the incidence of nephrotic syndrome complications, and the risk of adverse events associated with these immunosuppressive drug regimens. - Membranous nephropathy, immunosuppression, nephrotic syndrome, cyclophosphamide - Human Subjects